The AIDS virus, HIV, has been spreading worldwide at an alarming rate. Although significant progress has been made in the treatment of AIDS, it has been difficult to develop an effective HIV vaccine because the virus frequently mutates and because it can be transmitted through the mucosal route via sexual contact. Mucosal immunity in women's reproductive tracts has been documented to be an important first line of defense against HIV infection via heterosexual contact. But neither conventional vaccines nor oral vaccines are sufficient to induce mucosal immunity in the vagina. Therefore, the objective of this study is to test the feasibility of developing a bacterial vector-based vaccine capable of vaginal delivery. We hypothesize that women's vaginal lactobacilli can be engineered to deliver foreign antigens. We propose to: (i) establish gene-cloning systems in vaginal lactobacilli; and (ii) select gene-expression cassettes in vaginal lactobacilli for intracellular, extracellular and surface-bound expression of foreign antigens. We expect to document the feasibility of using vaginal lactobacilli to deliver foreign antigens. This study will be an important first step to attaining our long-term goal of developing a safe and effective mucosal vaccine delivery system to protect women against heterosexual HIV transmission.